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  • Ami Shah Lab

    Lab Website
    Principal Investigator:
    Ami Shah, M.D.
    Medicine

    Researchers in the Ami Shah Lab study scleroderma and Raynaud’s phenomenon. We examine the rela...tionship between cancer and scleroderma, with a focus on how and if cancer causes scleroderma to develop in some patients. We are currently conducting clinical research to study ways to detect cardiopulmonary complications in patients with scleroderma, biological and imaging markers of Raynaud’s phenomenon, and drugs that improve aspects of scleroderma. view more

    Research Areas: Raynaud's phenomenon, cancer, scleroderma, drugs, cardiovascular diseases
  • Anderson Lab

    Lab Website
    Principal Investigator:
    Mark Anderson, M.D., Ph.D.
    Medicine

    Research in the Anderson laboratory focuses on cellular signaling and ionic mechanisms that cau...se heart failure, arrhythmias and sudden cardiac death, major public health problems worldwide. Primary focus is on the multifunctional Ca2+ and calmodulin-dependent protein kinase II (CaMKII). The laboratory identified CaMKII as an important pro-arrhythmic and pro-cardiomyopathic signal, and its studies have provided proof of concept evidence motivating active efforts in biotech and the pharmaceutical industry to develop therapeutic CaMKII inhibitory drugs to treat heart failure and arrhythmias.

    Under physiological conditions, CaMKII is important for excitation-contraction coupling and fight or flight increases in heart rate. However, myocardial CaMKII is excessively activated during disease conditions where it contributes to loss of intracellular Ca2+ homeostasis, membrane hyperexcitability, premature cell death, and hypertrophic and inflammatory transcription. These downstream targets appear to contribute coordinately and decisively to heart failure and arrhythmias. Recently, researchers developed evidence that CaMKII also participates in asthma.

    Efforts at the laboratory, funded by grants from the National Institutes of Health, are highly collaborative and involve undergraduate assistants, graduate students, postdoctoral fellows and faculty. Key areas of focus are:
    • Ion channel biology and arrhythmias
    • Cardiac pacemaker physiology and disease
    • Molecular physiology of CaMKII
    • Myocardial and mitochondrial metabolism
    • CaMKII and reactive oxygen species in asthma

    Mark Anderson, MD, is the William Osler Professor of Medicine, the director of the Department of Medicine in the Johns Hopkins University School of Medicine and physician-in-chief of The Johns Hopkins Hospital.
    view more

    Research Areas: heart failure, arrhythmia, cardiovascular diseases, sudden cardiac death
  • Caleb Alexander Lab

    Lab Website
    Principal Investigator:
    G Alexander, M.D.
    Medicine

    Research in the Caleb Alexander Lab examines prescription drug use. This includes studies of po...pulation-based patterns and determinants of pharmaceutical use, clinical decision-making about prescription drugs, and the effect of changes in regulatory and payment policies on pharmaceutical utilization. We have special expertise in conducting survey-based studies and analyzing secondary data sources, including administrative claims, the Medical Expenditure Panel Survey and the National Ambulatory Medical Care Survey. view more

    Research Areas: epidemiology, medical decision making, drug safety, patient-provider relationships, pharmacoepidemiology, drugs
  • Charles W. Flexner Laboratory

    Principal Investigator:
    Charles Flexner, M.D.
    Medicine

    A. Laboratory activities include the use of accelerator mass spectrometry (AMS) techniques to m...easure intracellular drugs and drugs metabolites. AMS is a highly sensitive method for detecting tracer amounts of radio-labeled molecules in cells, tissues, and body fluids. We have been able to measure intracellular zidovudine triphosphate (the active anabolite of zidovudine) in peripheral blood mononuclear cells from healthy volunteers given small doses of 14C-zidovudine, and have directly compared the sensitivity of AMS to traditional LC/MS methods carried out in our laboratory.

    B. Clinical research activities investigate the clinical pharmacology of new anti-HIV therapies and drug combinations. Specific drug classes studied include HIV reverse transcriptase inhibitors, protease inhibitors, entry inhibitors (selective CCR5 and CXCR4 antagonists), and integrase inhibitors. Scientific objectives of clinical studies include characterization of early drug activity, toxicity, and pharmacokinetics. Additional objectives are characterization of pathways of drug metabolism, and identification of clinically significant harmful and beneficial drug interactions mediated by hepatic and intestinal cytochrome P450 isoforms.
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    Research Areas: antiretroviral drugs, infectious disease, HIV protease inhibitors, HIV, drugs, accelerator mass spectrometry
  • Craig W. Hendrix Lab

    Principal Investigator:
    Craig W. Hendrix, M.D.
    Medicine

    Research in the Craig W. Hendrix Lab concentrates on the chemoprevention of HIV infection, clin...ical pharmacology of antiviral drugs, drug interactions, and oral, topical and injectable HIV microbicide development. Our lab conducts small, intensive sampling studies of PK and PD of drugs for HIV prevention with a focus on developing methods to better understand HIV and drug distribution in the male genital tract, female genital tract and lower gastrointestinal tract. We also support numerous HIV pre-exposure prophylaxis development studies from phase I to phase III, largely as leader of the Pharmacology Core Laboratory of both the Microbicide Trial Network and HIV Prevention Trials Network. view more

    Research Areas: antiretroviral therapies, infectious disease, HIV, drugs
  • Dölen Lab

    Lab Website
    Principal Investigator:
    Gul Dolen, M.D., Ph.D.
    Neuroscience

    The Dölen lab studies the synaptic and circuit mechanisms that enable social behaviors. We use ...a variety of techniques including whole cell patch clamp electrophysiology, viral mediated gene transfer, optogenetics, and behavior. We are also interested in understanding how these synaptic and circuit mechanisms are disrupted in autism and schizophrenia, diseases which are characterized by social cognition deficits. More recently we have become interested in the therapeutic potential of psychedelic drugs for diseases like addiction and PTSD that respond to social influence or are aggravated by social injury, We are currently using both transgenic mouse and octopus to model disease. view more

    Research Areas: autism, PTSD, LSD, social behavior, Oxytocin, MDMA, neuroscience, psychedelics
  • Eric Nuermberger Lab

    Principal Investigator:
    Eric Nuermberger, M.D.
    Medicine

    Research in the Eric Nuermberger Lab focuses primarily on experimental chemotherapy for tubercu...losis. We use proven murine models of active and latent tuberculosis infection to assess the effectiveness of novel antimicrobials. A key goal is to identify new agents to combine with existing drugs to shorten tuberculosis therapy or enable less frequent drug administration. We're also using a flow-controlled in vitro pharmacodynamic system to better understand the pharmacodynamics of drug efficacy and the selection of drug-resistant mutants during exposure to current agents. view more

    Research Areas: pharmacodynamics, chemotherapy, infectious disease, antimicrobials, drugs, antibiotics, Streptococcus pneumoniae, pneumonia, tuberculosis
  • Frueh Laboratory

    Lab Website
    Principal Investigator:
    Dominique Frueh, Ph.D.
    Biophysics and Biophysical Chemistry

    The Frueh Laboratory uses nuclear magnetic resonance (NMR) to study how protein dynamics can be... modulated and how active enzymatic systems can be conformed. Non-ribosomal peptide synthetases (NRPS) are large enzymatic systems that biosynthesize secondary metabolites, many of which are used by pharmaceutical scientists to produce drugs such as antibiotics or anticancer agents. Dr. Frueh's laboratory uses NMR to study inter- and intra-domain modifications that occur during the catalytic steps of NRPS. Dr. Frueh and his team are constantly developing new NMR techniques to study these complicated enzymatic systems. view more

    Research Areas: enzymes, proteomics, imaging, drugs, antibiotics, nuclear magnetic resonance, molecular biology
  • Gabsang Lee Lab

    Principal Investigator:
    Gabsang Lee, Ph.D.
    Neurology

    Human induced pluripotent stem cells (hiPSCs) provide unprecedented opportunities for cell repl...acement approaches, disease modeling and drug discovery in a patient-specific manner. The Gabsang Lee Lab focuses on the neural crest lineage and skeletal muscle tissue, in terms of their fate-determination processes as well as relevant genetic disorders.

    Previously, we studied a human genetic disorder (familial dysautonomia, or FD) with hiPSCs and found that FD-specific neural crest cells have low levels of genes needed to make autonomous neurons--the ones needed for the "fight-or-flight" response. In an effort to discover novel drugs, we performed high-throughput screening with a compound library using FD patient-derived neural crest cells.

    We recently established a direct conversion methodology, turning patient fibroblasts into "induced neural crest (iNC)" that also exhibit disease-related phenotypes, just as the FD-hiPSC-derived neural crest. We're extending our research to the neural crest's neighboring cells, somite. Using multiple genetic reporter systems, we identified sufficient cues for directing hiPSCs into somite stage, followed by skeletal muscle lineages. This novel approach can straightforwardly apply to muscular dystrophies, resulting in expandable myoblasts in a patient-specific manner.
    view more

    Research Areas: stem cells, human-induced pluripotent stem cells, genomics, drugs, muscular dystrophy, familial dysautonomia
  • Intestinal Chloride Secretion

    Principal Investigator:
    Ming-Tseh Lin, M.D., Ph.D.
    Medicine

    Intestinal chloride secretion is stimulated during diarrhea. Cholera toxin is secreted by bacte...rium Vibrio cholera and is responsible for the watery diarrhea after cholera infection. Mechanistically, cholera toxin increases intracellular cyclic AMP, which subsequently activates protein kinase A and the cystic fibrosis transmembrane regulator chloride channel (CFTR).

    However, we recently identified an intestinal cAMP-Ca cross-talk signaling pathway that is initiated by elevation of intracellular cAMP and subsequently elevates intracellular Ca concentrations through the exchange protein activated by cAMP (Epac). This observation suggests that both CFTR and calcium-activated chloride channels are targets of elevated intracellular cAMP signaling molecule.

    Therefore, we are studying the role of calcium-activated Cl channels in intestinal chloride secretion under physiological conditions and during diarrhea. We are also determining whether the recently identified transmembrane protein 16 family of proteins, which are calcium-activated chloride channels, is also involved in intestinal chloride secretion in addition to the well characterized CFTR channel.

    Increased understanding of regulation of intestinal Cl secretion provides the necessary background information for the development of therapeutic drugs for the treatment of diarrhea, constipation and cystic fibrosis. The discovery that calcium-activated chloride channels are involved in intestinal chloride secretion provides additional targets for anti-diarrhea drug development.
    view more

    Research Areas: gastroenterology, diarrhea
  • Jodi Segal Lab

    Principal Investigator:
    Jodi Segal, M.D., M.P.H.
    Medicine

    Research in the Jodi Segal Lab focuses on developing methodologies to use observational data to... understand the use of new drugs, particularly drugs for treating diabetes, blood disorders and osteoporosis. We apply advanced methods for evidence-based review and meta-analysis, and—in collaboration with Johns Hopkins biostatisticians—we have developed new methodologies for observational research (using propensity scores to adjust for covariates that change over time) and methods to account for competing risks and heterogeneity of treatment effects in analyses. view more

    Research Areas: blood disorders, osteoporosis, diabetes, drugs, evidence-based medicine
  • John Schroeder Lab

    Principal Investigator:
    John Schroeder, Ph.D.
    Medicine

    The John Schroeder Lab focuses on understanding the role human basophils and mast cells play in... allergic reactions, as it relates not only to their secretion of potent inflammatory mediators (e.g., histamine and leukotriene C4) but also to their production of pro-inflammatory cytokines. We have long utilized human cells rather than cell lines in order to address the parameters, signal transduction and pharmacological aspects underlying clinically relevant basophil and mast cell responses. As a result, the lab has established protocols for rapidly isolating large numbers of basophils at high purity from human blood and for growing culture-derived mast cells/basophils from human progenitor cells. A variety of assays and techniques are also in place for concurrently detecting cytokines and mediators following a wide range of stimuli. These have facilitated the in vitro testing of numerous anti-allergic drugs for inhibitory activity on basophil and mast cell activation. The lab also studies counter-regulation between the IgE and innate immune receptors on human immature dendritic cell subtypes. view more

    Research Areas: cell biology, allergies, inflammation
  • Jun O. Liu Laboratory

    Lab Website

    The Jun O. Liu Laboratory tests small molecules to see if they react in our bodies to find pote...ntial drugs to treat disease. We employ high-throughput screening to identify modulators of various cellular processes and pathways that have been implicated in human diseases from cancer to autoimmune diseases. Once biologically active inhibitors are identified, they will serve both as probes of the biological processes of interest and as leads for the development of new drugs for treating human diseases. Among the biological processes of interest are cancer cell growth and apoptosis, angiogenesis, calcium-dependent signaling pathways, eukaryotic transcription and translation. view more

    Research Areas: cancer, autoimmune, eukaryotic cells, drugs, cellular signaling, pharmacology, calcium-dependent signaling pathways, molecular biology, angiogenesis
  • Kelly E. Dooley Laboratory

    Lab Website

    Research focuses on clinical pharmacology of new anti-tuberculosis regimens with an emphasis on...: (1) Phase I clinical trials of new or existing anti-TB drugs including dose escalation trials and studies of drug-drug interactions between anti-TB agents and antiretrovirals to treat HIV; (2) Use of PK/PD analysis and modelling in Phase II tuberculosis clinical treatment trials to determine concentration-effect relationships that will allow for optimization of dosing; and (3) Evaluation of TB and HIV drug concentrations in special populations, such as pregnant women and children; (4) Evaluation of treatment-shortening regimens for drug-sensitive TB and investigational regimens for treatment of multidrug-resistant TB; and (5) Translational work involving novel animal models of cavitary pulmonary TB disease to understand drug distribution in diseased lung. view more

    Research Areas: anti-infective drugs, antiretroviral therapies, tuberculosis and HIV treatments, HIV, lung disease, pharmacology, tuberculosis
  • Michael Kornberg Lab

    Lab Website

    Our laboratory conducts basic and translational research aimed at better understanding the path...ogenesis of multiple sclerosis (MS) and the role of the immune system in CNS disease, particularly the processes that drive progressive disability such as neurodegeneration and remyelination failure. We currently have three parallel research programs: 1. Metabolism as a modulator of MS: We are studying how basic metabolic pathways regulate the immune system and how these pathways might be exploited to protect neurons and myelin-forming oligodendrocytes from injury. 2. Identifying pathways by which nitric oxide (NO) and other free radicals cause neuronal and axonal damage. Our lab is identifying specific signaling pathways initiated by NO and other free radicals that can be targeted by drugs to produce neuroprotection. 3. Modulating the innate immune system in MS: In collaboration with others at Johns Hopkins, we are studying ways to enhance the reparative functions of microglia while preventing maladaptive responses. This work has identified bryostatin-1 as a potential drug that may be re-purposed for this task. view more

    Research Areas: multiple sclerosis
  • Namandje N. Bumpus Lab

    Lab Website
    Principal Investigator:
    Namandje Bumpus, Ph.D.
    Medicine

    The Bumpus Laboratory uses mass spectrometry and molecular pharmacology-based approaches to stu...dy the biotransformation of clinically used drugs by the cytochromes P450s. Specifically, we are studying ways to define a role for cytochrome P450-dependent metabolites in the drug-induced acute liver failure that is associated with certain antiviral drugs used to treat HIV and hepatitis C. Our long-term goal is to gain information that can be used to develop therapies that are devoid of toxic events by preventing the formation of a toxic metabolite or by developing strategies for preventing toxicity using concomitant therapy. view more

    Research Areas: antiviral therapy, drug metabolism, mass spectrometry, HIV, drugs, cellular signaling, cytochromes P450, pharmacology, molecular pharmacology, hepatitis C, metabolomics
  • Robert Siliciano Laboratory

    Principal Investigator:
    Robert Siliciano, M.D., Ph.D.
    Medicine

    Research in the Robert Siliciano Laboratory focuses on HIV and antiretroviral therapy (ART). AR...T consists of combinations of three drugs that inhibit specific steps in the virus life cycle. Though linked to reduced morbidity and mortality rates, ART is not curative. Through our research related to latently infected cells, we've shown that eradicating HIV-1 infection with ART alone is impossible due to the latent reservoir for HIV-1 in resting CD4+ T cells.

    Our laboratory characterized the different forms of HIV-1 that persist in patients on ART. Currently, we are searching for and evaluating drugs that target the latent reservoir. We are also developing assays that can be used to monitor the elimination of this reservoir. We are also interested in the basic pharmacodynamic principles that explain how antiretroviral drugs work. We have recently discovered why certain classes of antiretroviral drugs are so effective at inhibiting viral replication. We are using this discovery along with experimental and computational approaches to develop improved therapies for HIV-1 infection and to understand and prevent drug resistance. Finally, we are studying the immunology of HIV-1 infection, and in particular, the ability of some patients to control the infection without ART.
    view more

    Research Areas: antiretroviral therapies, HIV, drugs, pharmacology, drug resistance, T cells
  • Solomon Snyder Laboratory

    Lab Website

    Information processing in the brain reflects communication among neurons via neurotransmitters.... The Solomon Snyder Laboratory studies diverse signaling systems including those of neurotransmitters and second messengers as well as the actions of drugs upon these processes. We are interested in atypical neurotransmitters such as nitric oxide (NO), carbon monoxide (CO), and the D-isomers of certain amino acids, specifically D-serine and D-aspartate. Our discoveries are leading to a better understanding of how certain drugs for Parkinson's disease and Hungtington's disease interact with cells and proteins. Understanding how other second messengers work is giving us insight into anti-cancer therapies. view more

    Research Areas: Huntington's disease, amino acids, neurotransmitters, brain, cancer, nitric oxide, drugs, carbon monoxide, Parkinson's disease, nervous system
  • The Hillel Lab

    Lab Website

    The Hillel Laboratory at Johns Hopkins investigates inflammatory, genetic, and molecular factor...s involved with laryngotracheal stenosis, or scar formation in the airway. Specifically, we are examining the interrelationship between genetics, the immune system, bacteria, and scar formation in the airway. The lab has developed unique models to study laryngotracheal stenosis and test drugs that may halt the progression of scar or reverse scar formation. We are also developing a drug-eluting stent to treat patients with laryngotracheal stenosis. view more

    Research Areas: complex airway disorders, laryngotracheal stenosis
  • Theresa Shapiro Laboratory

    Principal Investigator:
    Theresa Shapiro, M.D., Ph.D.
    Medicine

    The Theresa Shapiro Laboratory studies antiparasitic chemotherapy. On a molecular basis, we are... interested in understanding the mechanism of action for existing antiparasitic agents, and in identifying vulnerable metabolic targets for much-needed, new, antiparasitic chemotherapy. Clinically, our studies are directed toward an evaluation, in humans, of the efficacy, pharmacokinetics, metabolism and safety of experimental antiparasitic drugs. view more

    Research Areas: sleeping sickness, infectious disease, drugs, malaria, pharmacology, antiparasitic chemotherapy, molecular biology
  • Vascular Neurology Lab

    Lab Website
    Principal Investigator:
    Rafael Tamargo, M.D.
    Neurology
    Neurosurgery

    Vascular research led by Rafael Tamargo, M.D., the Walter E. Dandy Professor of Neurosurgery, e...xplores treatment of aneurysms, arteriovenous malformations, cavernous malformations, and arteriovenous fistulas of the brain and spinal cord. Basic science research has focused on endothelial cell-leukocyte interactions (inflammation) after subarachnoid hemorrhage and identifying drugs that might inhibit this inflammatory response as well as the narrowing of blood vessels. view more

    Research Areas: aneurysm, stroke
  • William Bishai Laboratory

    Lab Website
    Principal Investigator:
    William Bishai, M.D., Ph.D.
    Medicine

    The William Bishai Laboratory studies the molecular pathogenesis of tuberculosis. The overall g...oal of our laboratory is to better understand tuberculosis pathogenesis and then to employ this understanding toward improved drugs, vaccines and diagnostics. Since Mycobacterium tuberculosis senses and adapts to a wide array of conditions during the disease process, it is clear that the regulation of expression of virulence factors plays an important role in pathogenesis. As a result, a theme of our research is to assess mycobacterial genes important in gene regulation. We are also interested in cell division in mycobacteria and the pathogenesis of caseation and cavitation. view more

    Research Areas: vaccines, genomics, drugs, pathogenesis, tuberculosis
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